Neuronal and vascular pathology produced by verocytotoxin 2 in the rabbit central nervous system

Abstract

To study the pathogenesis of the central nervous system (CNS) involvement associated with verocytotoxin-producing Escherichia coli infection, we developed an animal model by administering verocytotoxin 2 to rabbits either intravenously or intrathecally. After an interval of 2-9 days, the rabbits became paralyzed in a dose-dependent manner and in the absence of renal impairment. The minimal intravenous and intrathecal doses that produced these neurological signs were 250 and 0.4 ng/kg, respectively. After intravenous administration, most of the toxin was cleared from the serum within 24 h, with concomitant transition of a small amount into the cerebrospinal fluid. Pathological examination revealed that neurons in various CNS regions showed atrophy, cytoplasmic hyperchromasia and nuclear pyknosis as early as 6 h after administration. The distribution of affected neurons was constant and irrespective of the route of administration. Abnormalities of the blood vessels, such as the thickening of arterioles walls, were noted from 2 days after administration. The vascular lesions became more prominent after the intrathecal injection, which caused thrombosis and multiple infarction. Selective deposition of the toxin on the vessel walls was demonstrated immunohistochemically. Thus, the pathological manifestations of verocytotoxin 2 neurotoxicity consisted essentially of two types of lesions, early neuronal and late vascular, both of which might have developed under the influence of the toxin that had entered the CNS by crossing or circumventing the blood-brain barrier.

Escherichia coli O157:H7 Causes More-Severe Systemic Disease in Suckling Piglets than in Colostrum-Deprived Neonatal Piglets

“…Surprisingly, the incidence and severity of EHEC-induced clinical neurological signs were greater and these signs appeared earlier in suckling piglets than they do in CD piglets (6,10,13,18). Diarrhea occurred less frequently in suckling piglets than it does in juvenile rabbits (20), mice (16), and CD calves or piglets (6,7,11,12,18,22) inoculated with EHEC O157:H7 or Stx2 only. The presence of CNS signs in suckling piglets before they developed diarrhea may be evidence that Stx2 was absorbed before extensive intestinal damage occurred.…”

A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli O157:H7

“…For histologic examination, some of the paraffinembedded sections were stained with hematoxylin and eosin; and others, with luxol fast blue and cresyl violet. Immunohistologic localization of Stx2 was detected by a rabbit polyclonal antibody against Stx2, as described (18).…”

“…Stx2 causes multifocal vascular damage in the central nervous system, which is closely related to its morbidity and mortality in animal models (3,18,19,(22)(23)(24). Therefore, pathological changes in cerebral blood vessels, such as congestion and hemorrhage, were investigated after the i.v.…”

Characterization of a Shiga‐Toxin 1‐Resistant Stock of Vero Cells

“…In addition, renal tubular epithelial cells (5,8,12), mesangial cells (33,40), macrophages/monocytes (37,39), and neuronal cells (20,30), all of which express Gb3Cer, have also been found to be directly affected by Stx. In addition to normal cells, a number of cell lines have been reported to be sensitive to Stx cytotoxicity.…”